The long-term goal of this research project is to understand how regulatory genes control cell fate choice during central nervous system (CNS) development. The powerful genetics, cell biology, molecular biology, and transgenic techniques of Drosophila melanogaster will be utilized to study the development of the cells that lie along the midline of the CNS. The CNS midline cells are an experimentally simple system consisting of a small number of neurons and glia whose formation can be readily visualized and studied. Besides their roles as functional neurons and glia, they also act as a signaling center that controls axonogenesis and formation of numerous CNS and non-CNS cell types. It is proposed that the Single-minded:Tango bHLH- PAS transcription factor complex interacts combinatorially with segment polarity gene products, HMG proteins, POU homeobox proteins and other factors to specify midline neural and glial cell fates. The aims of the project are three-fold: (1) describe how Single-minded:Tango interacts with other regulatory proteins to control midline precursor and glial cell transcription, (2) study how segment polarity gene products control the specification of midline precursor cells into midline neurons and glia, and (3) use array and enhancer trap technologies to describe global patterns of midline gene expression and how they are regulated. Together, these approaches will begin to provide a comprehensive view of the molecular control of CNS midline cell transcription and cell fate specification. Given the functional similarities in nervous system development between Drosophila and mammals, insight from this project will advance the mechanistic understanding of transcriptional control, neurogenesis, human birth defects, and obesity.